Marelim

Package leaflet: Information for the user

Marelim, 360 mg, enteric-coated tablets
Acidum mycophenolicum
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm someone else even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet:

1. What Marelim is and what it is used for
2. What you need to know before taking Marelim
3. How to take Marelim
4. Possible side effects
5. How to store Marelim
6. Contents of the pack and other information

1. What Marelim is and what it is used for

Marelim contains a substance called mycophenolic acid. It belongs to a group of medicines known as immunosuppressants.
Marelim is used to prevent rejection of a transplanted kidney by suppressing the activity of the immune system. It is used in combination with other medicines containing cyclosporine and corticosteroids.

2. Important information before taking Marelim

WARNING
Mycophenolic acid causes congenital malformations and miscarriage. Female patients who may become pregnant must
present a negative pregnancy test result before starting treatment and must follow the contraception advice given by their physician.
The doctor will discuss with the patient and provide written materials specifically addressing the effects of
mycophenolic acid on the unborn child. These materials should be carefully read and followed.
If the information provided is not fully understood, the patient should ask the physician for further clarification before taking mycophenolate. See also further information in this section under "Warnings and precautions" and "Pregnancy and breastfeeding".

When not to take Marelim

• if the patient is allergic to mycophenolic acid, sodium mycophenolate, mycophenolate mofetil, or any of the other ingredients of this medicine (listed in section 6);
• if the patient may become pregnant and has not presented a negative pregnancy test result before first use of the medicine, because mycophenolate causes congenital malformations and miscarriage;
• if the patient is pregnant or plans to become pregnant, or thinks she may be pregnant;
• if the patient is not using effective contraceptive methods (see also section "Contraception in women and men");
• if the patient is breastfeeding (see also section "Pregnancy and breastfeeding").

If any of the above points apply to the patient, the patient must inform the doctor before taking Marelim.

Warnings and precautions
Before starting treatment with Marelim, discuss the following with the doctor, pharmacist, or nurse:

• if the patient has or has ever had severe gastrointestinal disorders, such as peptic ulcer;
• if the patient has a rare inherited deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), such as Lesch-Nyhan syndrome or Kelley-Seegmiller syndrome.

The patient should be aware that:

• Marelim weakens the body's natural defense mechanisms against sunlight. Therefore, the risk of developing skin cancer is increased. Exposure to sunlight and ultraviolet (UV) radiation should be limited by wearing protective clothing and regularly applying sunscreen with a high protection factor. Advice on sun protection should be sought from the doctor.
• If the patient has previously had hepatitis B or C, Marelim may increase the risk of reactivation of these diseases. The doctor may order blood tests and monitor for symptoms of these conditions. If any symptoms occur (yellowing of the skin or eyes, nausea, loss of appetite, dark urine), the patient must inform the doctor immediately.
• If the patient develops a persistent cough or shortness of breath, especially if taking other immunosuppressive medicines, the patient must inform the doctor immediately.
• The doctor may order blood tests to measure antibody levels during treatment with Marelim, particularly in cases of recurrent infections, especially if the patient is also taking other immunosuppressive medicines. Based on test results, the doctor will decide whether treatment with Marelim should continue.
• If the patient develops any signs of infection (such as fever or sore throat) or unexpected bruising or bleeding, the patient must contact the doctor immediately.
• During treatment with Marelim, the doctor may order blood tests to monitor white blood cell count and will inform the patient whether treatment with Marelim can be continued.
• The active substance, mycophenolic acid, is not the same as other similarly named substances such as mycophenolate mofetil. These should not be used interchangeably without a doctor's instruction.
• Use of Marelim during pregnancy may harm the fetus (see also section "Pregnancy and breastfeeding") and increase the risk of miscarriage.

Children and adolescents
Use of Marelim in children and adolescents is not recommended due to lack of data.

Elderly patients
Marelim may be used in elderly patients (65 years of age or older) without the need to adjust the usual recommended dose.

Marelim with other medicines
The patient must inform the doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines planned for future use, including over-the-counter medicines.
In particular, the patient must inform the doctor if taking any of the following medicines:

• another immunosuppressive medicine, such as azathioprine or tacrolimus;
• medicines used to treat high blood cholesterol levels, such as cholestyramine;
• activated charcoal, used to treat gastrointestinal disorders such as diarrhoea, stomach upset, and gas;
• medicines that neutralize stomach acid, containing magnesium and aluminium;
• antiviral medicines, such as acyclovir or ganciclovir.

The patient must also inform the doctor if planning to receive any vaccinations.
Patients must not donate blood during treatment with mycophenolic acid and for at least 6 weeks after stopping treatment.
Men must not donate sperm during treatment with mycophenolic acid and for at least 90 days after stopping treatment.

Marelim with food, drink and alcohol
Marelim may be taken with or without food. The patient should choose one method and continue taking the medicine in the same way each day to ensure consistent absorption.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, thinks she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before taking this medicine. The doctor will discuss the risks associated with pregnancy and alternative methods to prevent transplant rejection if:

• the patient plans to become pregnant;
• the patient has stopped menstruating or thinks she has stopped menstruating, has unusual menstrual bleeding, or suspects she is pregnant;
• the patient has had sexual intercourse without using an effective contraceptive method. If the patient becomes pregnant while taking mycophenolate, she must inform her doctor immediately. However, the patient should continue taking Marelim until speaking with the doctor.

Pregnancy
Mycophenolate causes frequent miscarriages (50%) and severe congenital malformations (23–27%)
in unborn children. Reported congenital malformations include abnormalities of the ears, eyes, face (cleft lip/palate), fingers, heart, oesophagus (the tube connecting the throat to the stomach), kidneys, or the nervous system (e.g. spina bifida, a condition in which the spinal bones do not form properly). One or more of these malformations may occur in the patient's child.
Female patients capable of becoming pregnant must present a negative pregnancy test result before
starting treatment and must follow the contraception advice given by their physician. The doctor may request more than one pregnancy test to confirm that the patient is not pregnant before starting treatment.

Breastfeeding
Marelim must not be taken if the patient is breastfeeding. This is because a small amount of the medicine may pass into breast milk.

Contraception in women taking Marelim
Women who may become pregnant should use an effective contraceptive method while taking Marelim. This applies to the following periods:

• before starting treatment with Marelim;
• throughout the entire duration of treatment with Marelim;
• for 6 weeks after stopping treatment with Marelim.

The patient should discuss with the doctor the choice of the most suitable contraceptive method. The choice of contraceptive method depends on the individual patient's circumstances. It is best for the patient to use two contraceptive methods simultaneously, as this reduces the risk of unintended pregnancy. The patient should contact the doctor as soon as possible if she thinks her contraceptive method may have failed or if she forgot to take a contraceptive pill.

A woman is considered unable to become pregnant if any of the following apply:

• she is postmenopausal, i.e. is at least 50 years old and her last menstrual period occurred more than one year ago (if menstruation stopped due to anticancer treatment, pregnancy may still be possible);
• she has undergone surgical removal of both fallopian tubes and both ovaries (bilateral salpingo-oophorectomy);
• she has undergone surgical removal of the uterus (hysterectomy);
• her ovaries have ceased functioning (premature ovarian failure, confirmed by a specialist gynaecologist);
• she has one of the following rare congenital conditions that prevent pregnancy: XY genotype, Turner syndrome, or uterine agenesis;
• she is a child or adolescent who has not yet started menstruating.

Contraception in men taking Marelim
Available data do not indicate an increased risk of miscarriage or congenital malformations in children fathered by men taking mycophenolate. However, this risk cannot be completely ruled out.
As a precautionary measure, it is recommended that the patient or his partner use effective contraception during treatment and for at least 90 days after stopping treatment with Marelim.
If the patient plans to have a child, he should discuss potential risks with the doctor.

Driving and using machines
Marelim has minor influence on the ability to drive and use machines.

Marelim contains sodium
One enteric-coated tablet contains 27.9 mg of sodium (the main component of table salt). This corresponds to 0.7%
of the recommended maximum daily intake of sodium for an adult.

3. How to take Marelim

This medicine should always be taken as directed by the doctor. If in doubt, consult
your doctor or pharmacist. Marelim should only be prescribed by doctors experienced in managing
transplant patients.
What dose to take
The recommended daily dose of Marelim is 1440 mg (4 tablets of Marelim 360 mg), taken as two
separate doses of 720 mg each (2 tablets of Marelim 360 mg).
The tablets should be taken in the morning and in the evening.
The first 720 mg dose should be taken within 72 hours after transplantation.
In case of severe kidney function impairment
The daily dose should not exceed 1440 mg (4 tablets of Marelim 360 mg).
How to take Marelim
The tablets should be swallowed whole with a glass of water.
Do not break or crush the tablets.
Do not take tablets that have been crushed or divided.
Treatment should continue as long as immunosuppression is needed to prevent rejection of the
transplanted organ by the body.
If you take more Marelim than recommended
If more tablets of Marelim have been taken than recommended, or if someone else has taken the medicine,
seek immediate medical advice from your doctor or go to the nearest hospital. Medical assistance may be
required. Take the tablets with you and show them to the doctor or hospital staff. If the patient no longer
has the tablets, bring the empty packaging.
If you forget to take Marelim
If the patient forgets to take Marelim, they should take it as soon as possible, unless it is almost time
for the next dose. In that case, return to the regular dosing schedule. Consult your doctor. Do not take a
double dose to make up for a missed dose.
Stopping treatment with Marelim
Do not stop taking Marelim unless instructed by your doctor. Stopping treatment with Marelim may
increase the risk of rejection of the transplanted kidney by the body.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
In elderly patients, there may be a higher incidence of adverse reactions due to weakened
immune system function.
Immunosuppressive medicines, including Marelim, weaken the patient's natural defence mechanisms by suppressing organ transplant rejection. As a result, the body cannot fight infections as effectively as under normal conditions. Therefore, when taking Marelim, the patient is at increased risk of infections such as infections of the brain, skin, mouth, stomach and intestines, lungs, and urinary tract.
The treating physician will order regular blood tests to monitor any changes in blood cell counts or concentrations of substances transported in the blood, such as glucose, fats, and cholesterol.
Adverse reactions that may be serious:

• signs of infection including fever, chills, excessive sweating, feeling tired, drowsiness, or lack of energy. If the patient is taking Marelim, they may be more susceptible than usual to infections. This may
  affect various body systems, most commonly the kidneys, bladder, and upper and/or lower
  respiratory tract;

• vomiting blood, black or bloody stools, stomach or intestinal ulcer;

• swollen lymph nodes, new skin growths or enlargement of existing skin lesions, or changes in existing moles. Since this occurs in patients taking immunosuppressive medicines, a very small number of patients taking Marelim may develop skin cancer or lymph node cancer.

If any of the above symptoms occur after taking Marelim, contact a doctor immediately.
Other adverse reactions, including:
Very common (occurring in more than 1 in 10 patients)

• diarrhoea
• low white blood cell count
• low blood calcium levels (hypocalcaemia)
• low blood potassium levels (hypokalaemia)
• high blood uric acid levels (hyperuricaemia)
• high blood pressure (hypertension)
• joint pain (arthralgia)
• anxiety

Common (occurring in less than 1 in 10 patients)

• low red blood cell count, which may cause fatigue, shortness of breath, and pallor (anaemia)
• low platelet count, which may cause unexpected bleeding and bruising (thrombocytopenia)
• headache
• cough
• abdominal or stomach pain, inflammation of the stomach lining, bloating, constipation, indigestion, flatulence, loose stools, nausea, vomiting
• fatigue, fever
• abnormal kidney or liver function test results
• respiratory tract infections
• high blood potassium levels (hyperkalaemia)
• low blood magnesium levels (hypomagnesaemia)
• dizziness
• low blood pressure (hypotension)
• shortness of breath (dyspnoea)
• acne
• weakness (asthenia)
• muscle pain (myalgia)
• swelling of hands, ankles, or feet (peripheral oedema)
• itching

Uncommon (occurring in less than 1 in 100 patients)

• fast heartbeat (tachycardia) or irregular heartbeat (extra ventricular contractions), fluid in the lungs (pulmonary oedema)
• development of a fluid-filled cyst (lymphocele)
• tremor, difficulty sleeping
• redness and swelling of the eyes (conjunctivitis), blurred vision
• wheezing
• belching, foul breath, intestinal obstruction, lip ulceration, heartburn, discolouration of the tongue, dry mouth, gum inflammation, pancreatitis leading to severe upper abdominal pain, salivary duct blockage, peritonitis
• bone, blood, and skin infections
• blood in urine, kidney damage, pain and difficulty urinating
• hair loss, skin bruising
• joint inflammation, back pain, muscle cramps
• loss of appetite, increased lipid levels (hyperlipidaemia), glucose levels (diabetes), cholesterol levels (hypercholesterolaemia), or decreased blood phosphate levels (hypophosphataemia)
• flu-like symptoms (such as fatigue, chills, sore throat, joint and muscle pain), swelling of ankles and feet, pain, tremor, increased thirst, or weakness
• unusual dreams, hallucinations
• inability to achieve or maintain erection
• cough, difficulty breathing, painful breathing (possible symptoms of interstitial lung disease)

Frequency not known (frequency cannot be estimated from the available data)

• fever, sore throat, frequent infections with possible symptoms of lack of white blood cells in the blood (agranulocytosis)
• rash, itching, hives, shortness of breath or difficulty breathing, wheezing or cough, feeling faint, dizziness, changes in level of consciousness, hypotension with or without mild generalized itching, skin redness, and swelling of the face and/or throat (symptoms of a severe allergic reaction)

Other adverse reactions reported for medicines similar to Marelim
Additionally, the following adverse reactions have been reported in the class of medicines to which Marelim belongs: colitis (inflammation of the large intestine), cytomegalovirus-induced gastritis, intestinal wall perforation causing severe abdominal pain with possible bleeding, gastric or duodenal ulcers, low count of specific white blood cells or all blood cells, severe infections such as heart and heart valve infection and meningitis (infection of the membrane covering the brain and spinal cord), dyspnoea, cough, which may be due to bronchiectasis (a condition in which the airways are abnormally widened), and other less common bacterial infections usually causing severe lung diseases (tuberculosis and infection caused by atypical mycobacteria Mycobacterium). If a persistent cough or dyspnoea occurs, contact a doctor.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products at the address:
Al. Jerozolimskie 181C
PL-02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.
Adverse reactions can also be reported to the responsible entity.

5. How to store the medicinal product Marelim

Keep the medicinal product out of sight and reach of children.
Do not use this medicinal product after the expiry date stated on the carton.
The expiry date refers to the last day of the stated month.
No special temperature storage conditions apply to this medicinal product.
Store in the original packaging to protect from light.
Do not use this medicinal product if the packaging is damaged.
Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicinal products no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Marelim contains

• The active substance is mycophenolic acid (in the form of sodium mycophenolate). Each Marelim tablet contains 360 mg of mycophenolic acid.
• Other ingredients are:
  • Tablet core: microcrystalline cellulose, sodium croscarmellose, povidone K30, talc, colloidal anhydrous silica, magnesium stearate.
  • Enteric coating Acryl-Eze Pink 93O54222: copolymer of methacrylic acid and ethyl acrylate (1:1), talc, titanium dioxide (E 171), triethyl citrate, colloidal anhydrous silica, sodium bicarbonate, yellow iron oxide (E 172), red iron oxide (E 172), sodium lauryl sulfate.
  • Printing ink Opacode Black S-1-17823: shellac, black iron oxide (E 172), propylene glycol, ammonia.

What Marelim looks like and contents of the pack
Marelim is a peach-coloured, elongated, biconvex enteric-coated tablet with a black
imprint "M2" on one side and smooth on the other side.
Marelim is available in packs containing 50, 100, 120 or 250 tablets in blisters.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa Street 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer/Importer
STADA Arzneimittel AG
Stadastraße 2-18
61118 Bad Vilbel
Germany
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park,
Paola PLA 3000, Malta
Accord Healthcare Polska Sp. z o.o.,
Lutomierska Street 50, 95-200 Pabianice, Poland
Accord Healthcare B.V.
Winthontlaan 200
3526 KV Utrecht
The Netherlands
Accord Healthcare Single Member S.A.
64th Km National Road Athens,
Lamia, Schimatari, 32009
Greece

This medicinal product is authorised for sale in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names: